This is a competing renewal application for Years 11-15 of R01 DA12828, Cognitive Neuropsychology of HIV and Drug Abuse, an ongoing program of theory driven research to investigate the unique and additive effects of HIV and substance dependence on selected neurocognitive functions with neuroanatomical and functional significance for neuroAIDS research. During the current cycle we successfully demonstrated selective deficits among HIV+ drug users in measures of learning and executive functions critically dependent on basal ganglia and prefrontal cortex integrity. Our study findings provided unique evidence of significantly different patterns of neurocognitive performance among HIV+ male and female SDIs. Neurocognition among HIV+ women is significantly understudied and essentially no studies have compared neurocognitive performance of HIV+ men and women directly. Such studies are urgently needed for cocaine dependent HIV+ women, since cocaine dependence strongly and uniquely predicts morbidity and mortality among women living with HIV/AIDS and women are significantly more vulnerable to stimulant addiction compared with men. This renewal application will move forward by 1) comparing episodic memory and executive performance of HIV+ male and female cocaine dependent individuals 2)investigating potential interactive effects of severity of cocaine dependence with sex and serostatus on neurocognition; and 3) conducting an exploratory study of neurocognitive and hormonal fluctuation across the menstrual cycle as a prudent first step toward investigating potential female specific mechanisms of HIV-associated neurocognitive impairment among cocaine users. This application is uniquely positioned to acquire extensive knowledge directly relevant to neurobehavioral components of HIV disease management, cognitive strategies for enhancement of memory, cognitive recovery with continued abstinence from drugs and sex-appropriate relapse prevention strategies. Finally this application addresses research topics of high scientific priority for NIDA and will increase representation of women in studies of drug abuse. PUBLIC HEALTH RELEVANCE: Results from this study will characterize sex differences in memory and executive skills among HIV+ individuals with a history of cocaine dependence. These functions are frequently impaired among individuals with HIV-associated neurocognitive disorder (HAND) and also key components of addictive behavior. This new knowledge will facilitate design of sex-specific cognitive remediation and enhancement techniques for improving memory and executive functions among HIV+ substance dependent individuals; apply knowledge of sex differences in learning, memory and executive functions as potential improvements in sex-specific strategies of relapse prevention; and provide new knowledge of the effects of sex steroid hormones on neurocognitive function to fine tune somatic, social and behavioral interventions for cocaine dependent HIV+ women through the menstrual transition.